GLUT2, glucose sensing and glucose homeostasis
Open accessAbstract
The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.
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GLUT1 constitutes the primary glucose transporters in human β-cells, whereas Glut2 mediates glucose transport in mouse β-cells.
“In mice, this is mediated by Glut2 (Slc2a2), which has a low affinity for glucose (i.e. has a high Km) and a high transport capacity (682).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [682]
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BackgroundGlucose transporters in the 21st Century
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- Authors
- Thorens, B.
- Affiliations
- University of Lausanne (CH)
- Corresponding author
- Thorens, Bernard
- ORCID
- Thorens, Bernard
- Venue
- Diabetologia
- Published
- 2014-11-25
- Volume
- 58
- Issue
- 2
- Pages
- 221-232
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2046120487
- Cited by
- 722
- References
- 7
- Citations by year
- 2026: 44 · 2025: 69 · 2024: 89 · 2023: 85 · 2022: 99 · 2021: 80 · 2020: 84 · 2019: 52 · 2018: 41 · 2017: 38 · 2016: 30 · 2015: 11
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- RERO DOC (Universität Bern) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Seventh Framework Programme
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- GLUT2, glucose detection, glucose homeostasis, glucose-stimulated insulin secretion, pancreatic beta cells, hepatocytes, bile acids, nucleus tractus solitarius, glucagon secretion, hypoglycemia, Fanconi-Bickel syndrome, neonatal diabetes, type 2 diabetes risk, fasting hyperglycemia, cardiovascular risk, sugar preference, genetically modified mice
- MeSH terms
- Animals, Disease Models, Animal, Glucose, Homeostasis, Humans, Hyperglycemia, Insulin, Signal Transduction, Mutation, Missense, Polymorphism, Single Nucleotide, Glucose Transporter Type 2, Mice, Genome-Wide Association Study
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